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Agomelatin Yetişkin Sıçanlarda Skopolamin Kaynaklı Öğrenme ve Hafıza Bozukluğunu Tersine Çevirir

Yıl 2021, Cilt: 6 Sayı: 4, 535 - 541, 01.12.2021
https://doi.org/10.26453/otjhs.975452

Öz

Amaç: Agomelatin, melatonin reseptör (MT1 ve MT2) agonisti ve serotonin reseptör (5-HT2C) antagonisti olan antidepresan bir ilaçtır. Artan kanıtlar, agomelatinin nöroprotektif ve nöromodülatör etkiye sahip olduğunu göstermektedir. Bu çalışmada skopolamin indüklü bilişsel yetmezlik oluşturulan sıçanlarda agomelatinin potansiyel etkileri araştırılmıştır.
Materyal ve Metot: Erişkin erkek sıçanlara 21 gün süreyle skopolamin (1 mg/kg) ve agomelatin (40 mg/kg) uygulandı. İlaç uygulamalarını takiben sıçanlar bilişsel davranışların değerlendirilebilmesi amacıyla yeni nesne tanıma (YNT) ve Morris su labirenti (MSL) testine tabi tutuldu. İlave olarak, beyin nörokimyasal analizleri için hipokampus ve prefrontal kortekste beyin-türevi nörotrofik faktör (BDNF) ve asetilkolin (ACh) düzeyleri değerlendirildi.
Bulgular: Skopolamin hem uzamsal hafızayı hem de ayırt etme indeksini önemli ölçüde azalttı (p<0,05). Agomelatin tedavisi uzamsal hafıza performansını ve keşif süresini arttırdı, ancak ayrımcılık indeksini etkilemedi (P>0,05). Ayrıca agomelatin, skopolamin grubuna kıyasla hem hipokampusta hem de prefrontal kortekste BDNF düzeylerini önemli ölçüde arttırdı (sırasıyla p<0,05, p<0,01). Diğer yandan grupların ACh düzeyleri arasında istatistiksel olarak anlamlılık bulunmadı (p>0,05).
Sonuç: Birlikte ele alındığında, bu sonuçlar agomelatinin skopolamin kaynaklı hafıza yetmezliğinin hafifletilmesinde belirgin rol oynadığını göstermiştir. Bu nedenle, agomelatinin bilişsel yetmezliğin önlenmesinde potansiyel bir ajan olabileceğini öne sürüyoruz.  

Kaynakça

  • Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer ’ s disease. 2019;5:1-18.
  • Grimm A, Mensah-Nyagan AG, Eckert A. Alzheimer, mitochondria and gender. Neurosci Biobehav Rev. 2016;67:89-101. doi:10.1016/j.neubiorev.2016.04.012
  • Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, De Andrade Paes AM. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol. 2018;9(OCT):1-14. doi:10.3389/fphar.2018.01192
  • Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35(6):1397-1409. doi:10.1016/j.neubiorev.2011.03.001
  • Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci Biobehav Rev. 2010;34(8):1307-1350. doi:10.1016/j.neubiorev.2010.04.001
  • Haider S, Tabassum S, Perveen T. Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study. Brain Res Bull. 2016;127:234-247. doi:10.1016/j.brainresbull.2016.10.002
  • Tota SK, Hanif K, Kamat PK, Najmi AK, Nath C. Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function. Psychopharmacology (Berl). 2012;222(2):185-202. doi:10.1007/s00213-012-2639-7
  • Lu C, Wang Y, Xu T, et al. Genistein ameliorates scopolamine-induced amnesia in mice through the regulation of the cholinergic neurotransmission, antioxidant system and the ERK/CREB/BDNF signaling. Front Pharmacol. 2018;9(OCT):1-11. doi:10.3389/fphar.2018.01153
  • Chen BH, Park JH, Lee TK, et al. Melatonin attenuates scopolamine-induced cognitive impairment via protecting against demyelination through BDNF-TrkB signaling in the mouse dentate gyrus. Chem Biol Interact. 2018;285(January):8-13. doi:10.1016/j.cbi.2018.02.023
  • Papp M, Gruca P, Boyer PA, Mocaer E. Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology. 2003;28(4):694-703. doi:10.1038/sj.npp.1300091
  • Rainer Q, Xia L, Guilloux JP, et al. Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol. 2012;15(3):321-335. doi:10.1017/S1461145711000356
  • Can ÖD, Üçel Uİ, Özkay ÜD, Ulupınar E. The effect of agomelatine treatment on diabetes-induced cognitive impairments in rats: Concomitant alterations in the hippocampal neuron numbers. Int J Mol Sci. Published online 2018. doi:10.3390/ijms19082461
  • Molteni R, Calabrese F, Pisoni S, et al. Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry. 2010;11(2):148-153. doi:10.3109/15622970903447659
  • Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
  • Martin V, Allaïli N, Euvrard M, et al. Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice. Sci Rep. 2017;8(March):1-11. doi:10.1038/srep45907
  • Gupta S, Singh P, Sharma B, Sharma B. Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia. Curr Neurovasc Res. 2015;12(3):240-252. doi:10.2174/1567202612666150603130235
  • Özkay ÜD, Söztutar E, Can ÖD, Üçel UI, Öztürk Y, Ulupinar E. Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats. Behav Pharmacol. Published online 2015. doi:10.1097/FBP.0000000000000153
  • Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res. Published online 1988. doi:10.1016/0166-4328(88)90157-X
  • Tian SW, Xu F, Gui SJ. Apelin-13 reverses memory impairment and depression-like behavior in chronic social defeat stressed rats. Peptides. Published online 2018. doi:10.1016/j.peptides.2018.08.009
  • Saral S, Topçu A, Alkanat M, et al. Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction. Behav Brain Res. 2021;408:113290. doi:10.1016/j.bbr.2021.113290
  • Jafarian S, Ling KH, Hassan Z, Perimal-Lewis L, Sulaiman MR, Perimal EK. Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats. Alzheimer’s Dement Transl Res Clin Interv. 2019;5:637-643. doi:10.1016/j.trci.2019.09.009
  • Janas AM, Cunningham SC, Duffy KB, et al. The cholinesterase inhibitor, phenserine, improves Morris water maze performance of scopolamine-treated rats. Life Sci. 2005;76(10):1073-1081. doi:10.1016/j.lfs.2004.06.028
  • Lee JC, Park JH, Ahn JH, et al. Effects of chronic scopolamine treatment on cognitive impairment and neurofilament expression in the mouse hippocampus. Mol Med Rep. 2018;17(1):1625-1632. doi:10.3892/mmr.2017.8082
  • Kim DH, Ryu JH. Differential effects of scopolamine on memory processes in the object recognition test and the Morris water maze test in mice. Biomol Ther. 2008;16(3):173-178. doi:10.4062/biomolther.2008.16.3.173
  • Ko YH, Kwon SH, Lee SY, Jang CG. Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling in the hippocampus and frontal cortex. Arch Pharm Res. 2019;42(8):722-731. doi:10.1007/s12272-019-01172-7
  • Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
  • Lu Y, Ho CS, McIntyre RS, Wang W, Ho RC. Agomelatine-induced modulation of brain-derived neurotrophic factor (BDNF) in the rat hippocampus. Life Sci. 2018;210(August):177-184. doi:10.1016/j.lfs.2018.09.003
  • Lee B, Shim I, Lee H, Hahm DH. Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats. J Microbiol Biotechnol. 2011;21(8):874-883. doi:10.4014/jmb.1104.04012
  • Klaassens BL, van Gerven JMA, Klaassen ES, van der Grond J, Rombouts SARB. Cholinergic and serotonergic modulation of resting state functional brain connectivity in Alzheimer’s disease. Neuroimage. 2019;199(October 2018):143-152. doi:10.1016/j.neuroimage.2019.05.044
  • Wong-Guerra M, Jiménez-Martin J, Fonseca-Fonseca LA, et al. JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment. Neurol Res. 2019;41(5):385-398. doi:10.1080/01616412.2019.1573285

Agomelatine Reverses Scopolamine-Induced Learning and Memory Impairment in Adult Rats

Yıl 2021, Cilt: 6 Sayı: 4, 535 - 541, 01.12.2021
https://doi.org/10.26453/otjhs.975452

Öz

Objective: The antidepressant agomelatine agent is a melatonin receptor (MT1 and MT2) agonist and a serotonin receptor (5-HT2C) antagonist. Increasing evidence shows that agomelatine has neuroprotective and neuromodulatory effects. In this study, the potential effects of agomelatine in rats with scopolamine-induced cognitive impairment were investigated.
Materials and Methods: Adult male rats were administered scopolamine (1 mg/kg) and agomelatine (40 mg/kg) for 21 days. After drug administration, rats were subjected to new object recognition (NOR) and Morris water maze (MWM) tests in order to evaluate cognitive behaviors. In addition, brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels in the hippocampus and prefrontal cortex were evaluated.
Results: Scopolamine significantly decreased both spatial memory and discrimination index (p<0.05). Agomelatine treatment increased spatial memory performance and exploration time, but did not affect the discrimination index (P>0.05). In addition, agomelatine significantly increased BDNF levels in both hippocampus and prefrontal cortex compared to the scopolamine group (p<0.05, p<0.01, respectively). On the other hand, there was no statistically significant difference between the ACh levels of the groups (p>0.05).
Conclusion: Taken together, these results demonstrated that agomelatine plays a important role in alleviating scopolamine-induced memory impairment. Therefore, we suggest that agomelatine may be a potential agent in the prevention of cognitive impairment.  

Kaynakça

  • Deture MA, Dickson DW. The neuropathological diagnosis of Alzheimer ’ s disease. 2019;5:1-18.
  • Grimm A, Mensah-Nyagan AG, Eckert A. Alzheimer, mitochondria and gender. Neurosci Biobehav Rev. 2016;67:89-101. doi:10.1016/j.neubiorev.2016.04.012
  • Dos Santos TC, Gomes TM, Pinto BAS, Camara AL, De Andrade Paes AM. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Front Pharmacol. 2018;9(OCT):1-14. doi:10.3389/fphar.2018.01192
  • Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35(6):1397-1409. doi:10.1016/j.neubiorev.2011.03.001
  • Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci Biobehav Rev. 2010;34(8):1307-1350. doi:10.1016/j.neubiorev.2010.04.001
  • Haider S, Tabassum S, Perveen T. Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: A comparative study. Brain Res Bull. 2016;127:234-247. doi:10.1016/j.brainresbull.2016.10.002
  • Tota SK, Hanif K, Kamat PK, Najmi AK, Nath C. Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function. Psychopharmacology (Berl). 2012;222(2):185-202. doi:10.1007/s00213-012-2639-7
  • Lu C, Wang Y, Xu T, et al. Genistein ameliorates scopolamine-induced amnesia in mice through the regulation of the cholinergic neurotransmission, antioxidant system and the ERK/CREB/BDNF signaling. Front Pharmacol. 2018;9(OCT):1-11. doi:10.3389/fphar.2018.01153
  • Chen BH, Park JH, Lee TK, et al. Melatonin attenuates scopolamine-induced cognitive impairment via protecting against demyelination through BDNF-TrkB signaling in the mouse dentate gyrus. Chem Biol Interact. 2018;285(January):8-13. doi:10.1016/j.cbi.2018.02.023
  • Papp M, Gruca P, Boyer PA, Mocaer E. Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology. 2003;28(4):694-703. doi:10.1038/sj.npp.1300091
  • Rainer Q, Xia L, Guilloux JP, et al. Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol. 2012;15(3):321-335. doi:10.1017/S1461145711000356
  • Can ÖD, Üçel Uİ, Özkay ÜD, Ulupınar E. The effect of agomelatine treatment on diabetes-induced cognitive impairments in rats: Concomitant alterations in the hippocampal neuron numbers. Int J Mol Sci. Published online 2018. doi:10.3390/ijms19082461
  • Molteni R, Calabrese F, Pisoni S, et al. Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry. 2010;11(2):148-153. doi:10.3109/15622970903447659
  • Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
  • Martin V, Allaïli N, Euvrard M, et al. Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice. Sci Rep. 2017;8(March):1-11. doi:10.1038/srep45907
  • Gupta S, Singh P, Sharma B, Sharma B. Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia. Curr Neurovasc Res. 2015;12(3):240-252. doi:10.2174/1567202612666150603130235
  • Özkay ÜD, Söztutar E, Can ÖD, Üçel UI, Öztürk Y, Ulupinar E. Effects of long-term agomelatine treatment on the cognitive performance and hippocampal plasticity of adult rats. Behav Pharmacol. Published online 2015. doi:10.1097/FBP.0000000000000153
  • Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res. Published online 1988. doi:10.1016/0166-4328(88)90157-X
  • Tian SW, Xu F, Gui SJ. Apelin-13 reverses memory impairment and depression-like behavior in chronic social defeat stressed rats. Peptides. Published online 2018. doi:10.1016/j.peptides.2018.08.009
  • Saral S, Topçu A, Alkanat M, et al. Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction. Behav Brain Res. 2021;408:113290. doi:10.1016/j.bbr.2021.113290
  • Jafarian S, Ling KH, Hassan Z, Perimal-Lewis L, Sulaiman MR, Perimal EK. Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats. Alzheimer’s Dement Transl Res Clin Interv. 2019;5:637-643. doi:10.1016/j.trci.2019.09.009
  • Janas AM, Cunningham SC, Duffy KB, et al. The cholinesterase inhibitor, phenserine, improves Morris water maze performance of scopolamine-treated rats. Life Sci. 2005;76(10):1073-1081. doi:10.1016/j.lfs.2004.06.028
  • Lee JC, Park JH, Ahn JH, et al. Effects of chronic scopolamine treatment on cognitive impairment and neurofilament expression in the mouse hippocampus. Mol Med Rep. 2018;17(1):1625-1632. doi:10.3892/mmr.2017.8082
  • Kim DH, Ryu JH. Differential effects of scopolamine on memory processes in the object recognition test and the Morris water maze test in mice. Biomol Ther. 2008;16(3):173-178. doi:10.4062/biomolther.2008.16.3.173
  • Ko YH, Kwon SH, Lee SY, Jang CG. Isoorientin improves scopolamine-induced cognitive impairments by restoring the cholinergic system, antioxidant defense, and p-CREB/BDNF signaling in the hippocampus and frontal cortex. Arch Pharm Res. 2019;42(8):722-731. doi:10.1007/s12272-019-01172-7
  • Gumuslu E, Mutlu O, Sunnetci D, et al. The antidepressant agomelatine improves memory deterioration and upregulates CREB and BDNF gene expression levels in unpredictable chronic mild stress (UCMS)-exposed mice. Drug Target Insights. 2014;2014(8):11-21. doi:10.4137/DTI.S13870
  • Lu Y, Ho CS, McIntyre RS, Wang W, Ho RC. Agomelatine-induced modulation of brain-derived neurotrophic factor (BDNF) in the rat hippocampus. Life Sci. 2018;210(August):177-184. doi:10.1016/j.lfs.2018.09.003
  • Lee B, Shim I, Lee H, Hahm DH. Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats. J Microbiol Biotechnol. 2011;21(8):874-883. doi:10.4014/jmb.1104.04012
  • Klaassens BL, van Gerven JMA, Klaassen ES, van der Grond J, Rombouts SARB. Cholinergic and serotonergic modulation of resting state functional brain connectivity in Alzheimer’s disease. Neuroimage. 2019;199(October 2018):143-152. doi:10.1016/j.neuroimage.2019.05.044
  • Wong-Guerra M, Jiménez-Martin J, Fonseca-Fonseca LA, et al. JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment. Neurol Res. 2019;41(5):385-398. doi:10.1080/01616412.2019.1573285
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makalesi
Yazarlar

Sinan Saral 0000-0002-0961-1903

Atilla Topçu 0000-0003-4730-5015

Ayşegül Sümer 0000-0003-4918-4368

Ali Koray Kaya 0000-0003-2433-5115

Aykut Öztürk 0000-0003-4515-6968

Esra Pınarbaş 0000-0001-6231-7597

Yayımlanma Tarihi 1 Aralık 2021
Gönderilme Tarihi 29 Temmuz 2021
Kabul Tarihi 21 Ekim 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 6 Sayı: 4

Kaynak Göster

AMA Saral S, Topçu A, Sümer A, Kaya AK, Öztürk A, Pınarbaş E. Agomelatine Reverses Scopolamine-Induced Learning and Memory Impairment in Adult Rats. OTSBD. Aralık 2021;6(4):535-541. doi:10.26453/otjhs.975452

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